Myotonic dystrophy (DM) is a highly variable multisystemic genetic disease and the commonest muscular dystrophy in adults. Such temporal and phenotypic variability poses particular challenges for ...clinical management and research. By collecting patient data, registries constitute fundamental tools to increase knowledge on rare diseases and to promote research. However, the benefit of collecting data in a real world setting can be counterbalanced by a lower completeness and quality of data. In DM, cognitive impairment further limits patients direct contribution and input from expert clinicians is required. We developed the DM-Scope registry system to gather most relevant clinical and epidemiological data in a large DM population. The general aim is to promote research and to improve clinical practice in the management of patients with DM. Multidisciplinary physicians from rare diseases reference centers use a concise and structured form during patients annual evaluation, while entering and monitoring of data are independently performed by the coordinating center resources. The system provides a permanent online secure access to own patients data and specific tools such as edition of severity graphs and disease synopsis. Other request applications can be used to screen those patients eligible for clinical studies or identifying available biomaterial at the Genethon biobank. The DM-Scope system is broadly used in 31 French neuromuscular centers, gathering up to 1600 DM patients and fully harmonized with the Quebec DM registry (1100 enrolled patients), i.e. the largest collection of standardized data from the myotonic dystrophy population. The registry already supports several ongoing clinical research studies, including natural history and outcome measures assessment studies. In the context of emerging therapeutic approaches, the DM-scope platform constitutes a powerful device to promote a synergic network and DM research in an international multicenter framework.
The correlation between the incidence of GVHD and the number of infused CD34(+) cells remains controversial for PBSC transplantation after a reduced-intensity-conditioning (RIC) regimen. We evaluated ...99 patients transplanted with an HLA-identical sibling after the same RIC (2-Gy-TBI/fludarabine). Donor and recipient characteristics, donor's blood G-CSF-mobilized CD34(+) cell count, and number of infused CD34(+) and CD3(+) cells were analyzed as risk factors for acute and chronic GVHD There was a trend for an increased incidence of extensive chronic GVHD in the quartile of patients receiving more than 10 × 10(6) CD34(+) cells/kg (P = 0.05). Interestingly, the number of donor's blood CD34(+) cells at day 5 of G-CSF mobilization was closely associated with the incidence of extensive chronic GVHD, that is, 48% (95% CI: 28-68) at 24-months in the quartile of patients whose donors had the highest CD34(+) cell counts versus 24.3% (95% CI: 14-34) in the other patients (P = 0.007). In multivariate analysis, the only factor correlating with extensive chronic GVHD (cGVHD) was the donor's blood CD34(+) cell count after G-CSF (HR 2.49; 95% CI: 1.16-5.35, P = 0.019). This study shows that the incidence of cGVHD is more strongly associated with the donor's ability to mobilize CD34(+) cells than with the number of infused CD34(+) cells.
Pulse pressure is a stronger predictor of cardiovascular events than systolic or diastolic blood pressure in large cohorts of French and North American patients. However, its influence on stroke is ...controversial. Large-artery stiffness is the main determinant of pulse pressure. The influence of arterial stiffness on the occurrence of stroke has never been demonstrated. Our aim was to establish the relationship between aortic stiffness and stroke death in hypertensive patients.
We included, in a longitudinal study, 1715 essential hypertensive patients who had a measurement of arterial stiffness at entry (ie, between 1980 and 2001) and no overt cardiovascular disease or symptoms. Mean follow-up was 7.9 years. At entry, aortic stiffness was assessed from the carotid-femoral pulse wave velocity. A Cox proportional hazard regression model was used to estimate the relative risk (RR) of stroke and coronary deaths.
Mean+/-SD age at entry was 51+/-13 years. Twenty-five fatal strokes and 35 fatal coronary events occurred. Pulse wave velocity significantly predicted the occurrence of stroke death in the whole population. There was a RR increase of 1.72 (95% CI, 1.48 to 1.96; P<0.0001) for each SD increase in pulse wave velocity (4 m/s). The predictive value of pulse wave velocity remained significant (RR=1.39 95% CI, 1.08 to 1.72; P=0.02) after full adjustment for classic cardiovascular risk factors, including age, cholesterol, diabetes, smoking, mean blood pressure, and pulse pressure. In this population, pulse pressure significantly predicted stroke in univariate analysis, with a RR increase of 1.33 (95% CI, 1.16 to 1.51) for each 10 mm Hg of pulse pressure (P<0.0001) but not after adjustment for age (RR=1.19 95% CI, 0.96 to 1.47; P=0.10).
This study provides the first evidence, in a longitudinal study, that aortic stiffness is an independent predictor of fatal stroke in patients with essential hypertension.
Abstract
Calcium scores of the coronary arteries (CCS) and – more recently – of the the thoracic aorta (TCS), have been established as risk markers for cardiovascular events. Yet, little is known ...about the relationship between these two calcium scores.
In this study, CCS and TCS were compared in 1010 patients with a normal SPECT. Mean age was 64.5±8.7 yrs with 73.4% of men. CCS and TCS ranged between 0 and 5827 for CCS and from 0 to 58600 for TCS, with means of 281.1 and 1206 respectively. Such a difference was expected since the vascular surface of the thoracic aorta is approximately 5 times larger than that of the coronary arterial tree. Both CCS and TCS increased with the number of risk factors (p=0.000841 and p=0.000579)
No significant relation was found between CCS and TCS for the entire group. However, when adopting a best-fitting curve model, 2 populations could be clearly identified: those with predominant TCS (N=552), and those with a- relatively- predominant CCS – (N=458).
In each of these two groups, CCS and TCS were significantly related (r=0.63 and 0.69 respectively p<2.2e-12). Both groups had a comparable exposition to smoking and diabetes, but Group1 patients had more dyslipemia and high blood pressure than group 2 patients.
Conclusion
Calcified atheroma was frequently observed In patients with a normal SPECT, but no significant relation existed between CCS and TCS; patients with a predominant atheroma of the coronary arteries were not the same than patients with a predominant atheroma of the aorta, with both groups having different expositions to risk factors. This suggests that atheroma of the coronary arteries and of the thoracic aorta are close but not identical diseases.
To study the impact of high-dose therapy (HDT) with autologous stem-cell support in patients with symptomatic multiple myeloma (MM) between the ages of 55 and 65 years.
One hundred ninety patients ...between 55 and 65 years old who had newly diagnosed stage II or III MM were randomly assigned to receive either conventional chemotherapy (CCT; ie, monthly courses of a regimen of vincristine, melphalan, cyclophosphamide, and prednisone) or HDT and autologous blood stem-cell transplantation (using either melphalan alone 200 mg/m(2) intravenous IV or melphalan 140 mg/m(2) IV plus busulfan 16 mg/kg orally as pretransplantation cytoreduction).
Within a median follow-up of 120 months, median event-free survival (EFS) times were 25 and 19 months in the HDT and CCT groups, respectively. Median overall survival (OS) time was 47.8 months in the HDT group compared with 47.6 months in the CCT group. A trend to better EFS (P = .07) was observed in favor of HDT, whereas OS curves were not statistically different (P = .91). The period of time without symptoms, treatment, and treatment toxicity (TwiSTT) was significantly longer for the HDT patients than for the CCT patients (P = .03).
With a median follow-up time of approximately 10 years, this randomized trial confirmed a benefit of HDT in terms of EFS and TwiSTT but did not provide evidence for superiority of HDT over CCT in OS of patients aged 55 to 65 years with symptomatic newly diagnosed MM.
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